The invention relates to devices and methods for the contamination-free transfer of biological specimens, for example from supply containers, into the microtiter plates or comparable processing devices used to process the specimens. Such contamination-free transfer systems for DNA samples are known for microtiter plates with 96 cavities; they are based on covers for the cavities which can be removed by pipetting robots.
It is known that laboratories replicating DNA samples by PCR are frequently contaminated by DNA, often during a transfer of DNA samples from the supply containers to the cavities of th e microliter plates in which PCR amplification is to take place. The transfer is particularly critical for non-amplified DNA samples before their PCR replication because very small impurities with only few DNA molecules are also amplified, but other types of biological specimens can also be damaged by contamination, for instance by digesting enzymes.
This problem can be remedied by a system which provides all the cavities of the microtiter plates with covers individually, which can be removed by a pipetting robot. The pipetting robot proceeds as follows: The pipetting head first picks up a new pipette tip from a supply, opens a supply container, removes sample fluid with the pipetting tip, removes the lid from a cavity of the microtiter plate, pipettes the fluid into the cavity, closes the cavity again with the cover, and discards the pipette tip. This process is repeated for all the supply containers.
The considerable success of this system indicates that the contaminations are transferred by aerosols in the air of the laboratory and that a brief opening of the cavities and quickly feeding the specimen in the pipette tip through the air does rarely lead to contamination.
However, this cover system is very slow and is so far only available for microtiter plates with 96 cavities. In the meantime biological specimens are processed in microtiter plates with 384, 1536 or even 3456 cavities. Systems are also used which do away with cavities in the microtiter plates and perform the processing of the specimens in vertical droplets on hydrophilic anchors in a hydrophobic environment. For these systems with a high processing density, contamination-free transfer of the specimens is not yet possible.
It is the objective of the invention to find devices and methods with which solutions with biomolecules can be transferred, for example from supply vessels to processing systems with a high processing density, for instance microtiter plates with a large number of cavities, without contaminating the specimens with airborne impurities from the laboratory.
The invention is directed to protecting the fluids in the processing volumes from being contaminated by the ambient laboratory air by covering them with a framed, slidable blind which has openings through which the specimens can be pipetted, and by feeding a contamination-free gas into the space under the blind. By sliding the blind the openings can be moved over any processing location. Contamination of the processing volumes under the pipetting openings is avoided by the contamination-free gas which is freely flowing out of the pipetting openings. The gas prevents access from contaminating aerosols. The gas can, for instance, be moistened to prevent the specimens from drying out. Dry gas can be used to deliberately dry the specimens.
A simple embodiment is a blind with one row of openings which can be moved over all row of processing volumes. Microtiter plates show n2 xc3x9796 processing volumes, n being an integer number, in a pattern of 8xc3x97n lines and 12xc3x97n rows. A microtiter plate with 1536 wells thus shows the wells in 32 rows at 48 lines each. A blind with 32 openings with diameters of 1.5 millimeter each will easily allow to use pipette heads with four pipettes (18 millimeter distances), 8 pipettes (9 millimeter distances), or 16 Pipettes (4.5 millimeter distances).
Another embodiment is the use of two blinds, on top of each other, both slidable independently. The openings can, for example, be arranged in the form of two rows in right angles in the two blinds, whereby the blinds can be slid at right angles to the two rows.
For the blinds it is possible, for example, to use simple foils which are guided laterally along slide grooves. The blinds can take the form of continuous strips but they can also be wound up on blind rolls. The movement can be created by motors and controlled digitally. Lateral rows of serrations (as with compact camera films) can guarantee precise positioning.